Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure

Our plain-English summary of Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure, by D.M. Bernstein, R.A. Rogers, R. Sepulveda, et al (Toxicology and Applied Pharmacology, 2015).

The study

• Authors: D.M. Bernstein, R.A. Rogers, R. Sepulveda, P. Kunzendorf, B. Bellmann, H. Ernst, O. Creutzenberg, J.I. Phillips
• Journal: Toxicology and Applied Pharmacology
• Published: 2015;283(1):20-34
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study was designed to provide an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake-dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6h/day for 5 days to either brake-dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake-dust or crocidolite asbestos. The chrysotile fibers were relatively biosoluble whereas the crocidolite asbestos fibers persisted through the life-time of the animal. This was reflected in the lung and the pleura where no significant pathological response was observed at any time point in the brake dust or chrysotile/brake dust exposure groups through 365 days post exposure. In contrast, crocidolite asbestos produced a rapid inflammatory response in the lung parenchyma and the pleura, inducing a significant increase in fibrotic response in both of these compartments. Crocidolite fibers were observed embedded in the diaphragm with activated mesothelial cells immediately after cessation of exposure. While no chrysotile fibers were found in the mediastinal lymph nodes, crocidolite fibers of up to 35 μm were observed. These results provide support that brake-dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung or the pleural cavity following short term inhalation.

Copyright © 2014. Published by Elsevier Inc.

In plain English

In this animal experiment, male Wistar rats breathed, nose-only, for 6 hours a day on 5 days, one of four things: filtered air (65 rats), dust ground from chrysotile-containing drum brake shoes with added chrysotile (100 rats), the brake dust alone (100 rats), or crocidolite asbestos (100 rats). They were followed for up to 365 days. Long fibers cleared from the lungs with estimated half-times of 42 days in the brake dust with chrysotile group and 29 days in the brake dust alone group. For crocidolite the half-time was over 1000 days. The brake dust groups showed slight build-up of particle-laden macrophages and no fiber-related lung findings. They showed no statistically significant differences from air controls in lung or visceral pleural connective tissue. Crocidolite caused interstitial lung fibrosis within 32 days, visceral pleural thickening and pleural fibrosis at 365 days. At 91 days, crocidolite fibers up to 35 micrometers were found in mediastinal lymph nodes. No chrysotile fibers were found there. The authors concluded that brake dust from chrysotile-containing brake drums would not initiate a pathological response in the lung or pleural cavity after short-term inhalation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal inhalation experiment: rats were exposed for 5 days and examined at time points up to 365 days after exposure ended.
• Who was studied: Male Wistar rats, 8 to 10 weeks old at exposure, in four groups: 65 air controls and 100 rats in each of the three exposed groups. Exposures and pathology were done at the Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
• Exposure: Group 1 breathed filtered air. Group 2 breathed dust ground from mid-1960s automotive drum brake shoes containing approximately 30% (by area) chrysotile, mixed with added chrysotile grade 5R04 (3.48 mg/m3; 1,007 WHO fibers/cm3; 189 fibers 20 micrometers or longer per cm3). Group 3 breathed the brake dust alone (1.52 mg/m3; 46 WHO fibers/cm3; 3.6 fibers 20 micrometers or longer per cm3). Group 4 breathed unground crocidolite asbestos from the Voorspoed mine, South Africa (6.34 mg/m3; 709 WHO fibers/cm3; 93 fibers 20 micrometers or longer per cm3). All exposures ran 6 hours a day for 5 days.
• Main results:
  • Estimated lung clearance half-times of long fibers were 29 days in the brake dust group and 42 days in the chrysotile and brake dust group.
  • In the crocidolite group, the lung clearance half-time of long fibers was greater than 1000 days.
  • By confocal microscopy of lung tissue, in both brake dust groups only one fiber longer than 20 micrometers was seen at 32 days and none thereafter.
  • Groups 2 and 3 (brake dust with chrysotile, brake dust alone) had no fiber-related histopathological findings through 365 days. They had slight accumulation of particle-laden macrophages from 7 through 91 days, which decreased later.
  • Lung connective tissue in the two brake dust groups showed no statistically significant trends compared with the air control group.
  • In the crocidolite group, lung inflammation from day 0 progressed to Wagner grade 4 interstitial fibrosis within 32 days. Pleural fibrosis was also observed at 365 days.
  • In the crocidolite group, mean lung connective tissue rose from 4.5 plus or minus 3.5 percent at day 0 to 14.7 plus or minus 12.7 percent at 91 days. It stayed at 13.5 plus or minus 8.9 percent at 365 days, about 5 times the air control at 91 days.
  • In the crocidolite group, mean visceral pleural wall thickness rose from 3.1 plus or minus 0.7 micrometers at day 14 to 5.8 plus or minus 0.8 micrometers at day 272. In air controls it ranged from 2.5 plus or minus 0.6 to 3.4 plus or minus 0.7 micrometers.
  • In the crocidolite group, connective tissue in the visceral pleura rose from 6.5 plus or minus 2.4 percent at day 14 to 16.1 plus or minus 9.4 percent at day 365. This was statistically different from the air control and brake dust groups (p less than 0.01).
  • Visceral pleural connective tissue in the two brake dust groups was not statistically different from the air control group.
  • At 91 days, no chrysotile fibers were found in the mediastinal lymph nodes of the two brake dust groups.
  • At 91 days, 58 crocidolite fibers up to 35 micrometers long were recovered from the mediastinal lymph nodes of the crocidolite group.
  • Immediately after exposure ended (day 0), crocidolite fibers were seen protruding from the diaphragm surface with nearby activated mesothelial cells. The brake dust groups looked similar to air controls.
• The authors' conclusion: The authors concluded that this rat study supports that brake dust from chrysotile-containing brake drums would not initiate a pathological response in the lung or the pleural cavity after short-term inhalation.
• Limitations the authors state:
  • The whole-lung digestion method could not tell where in the lung remaining long fibers were located, for example trapped in the lower airways.
  • For the diaphragm (parietal pleura), only the scanning electron microscopy images from day 0 were available and presented.
  • The snap-freezing process caused some minor contraction of the lung.
  • Standard errors for the crocidolite clearance half-times could not be calculated.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Auto mechanics and brake work, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Pleura, Chrysotile, Crocidolite, Deposition, Translocation, Brake Lining, Amphibole Group, Parenchyma.

Related studies

• Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results — D.M. Bernstein, R. Rogers, et al. (2014)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study — D.M. Bernstein, B. Toth, et al. (2018)
• Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2011)
• The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results — D.M. Bernstein, R.A. Rogers, et al. (2010)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2020)

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